Core B: Human Tissue Collection, Processing, and Repository Core Project Summary Circulating lymphocytes are easy to access and therefore have been intensively studied in human beings. In contrast, much less is known regarding the biology of tissue-resident human lymphocytes. This problem exists because of limited access to sufficient quantities of human tissues. The overarching goal of this U19 Project is to advance understanding of humoral immunity by evaluating B cells in eight different human tissues. Three projects and three scientific cores will collaborate to examine the responses of B cells in these tissues against bacterial, viral, and transplant antigens. Core B's objective is to eliminate the challenges associated with human tissue access in support of the U19 goals. The organizational and operational structure of Core B is innovative because a team with broad expertise (surgical, immunologic, cell biology, and biorepositories) will be aligned with the Alabama Organ Center (AOC). The AOC manages deceased organ donors for the purposes of tissue transplantation and is on the same campus as Core B. This structure will enable the collection of tissues from approximately 19 human donors per year. Further, Core B will isolate, quality control and store leukocytes in a biorepository. The rationale for this approach is that it will not only increase human tissue access, it will standardize the isolation and storage of high-quality leukocytes. The repository component will enable the projects and cores of this U19 to search this collection to find the ideal samples for each experiment. This setup also facilitates the collaborative aspects of this U19 by enabling all projects to understand which samples exist so that sharing can be prioritized to maximize sample value. In Specific Aim 1, we will collect tissues from deceased organ donors via the AOC. The objective of Specific Aim 2 is to isolate and cryopreserve leukocytes from the tissues. Lastly, Specific Aim 3 will establish a searchable biorepository of these samples with which to support the research objectives of the U19. The activities of Core B are significant because they will eliminate barriers that have prevented access to tissue-resident lymphocytes, and they will enable the comparison of antigen-specific B cells in multiple tissues collected from the same individual, as well as comparison to other individuals. Many of these investigations will be entirely novel.